We have previously demonstrated that the vasodilator reserve of the coronary microcirculation is reduced after ergonovine in patients with chest pain despite normal coronary angiograms in the absence of epicardial spasm, and term this disorder microvascular angina. We subsequently found limited flow response to ischemia in forearm vessels and abnormal esophageal motility, suggesting a widespread disorder of smooth muscle tone. Because dyspnea is common in these patients and seems disproportionate to the severity of myocardial ischemia, we studied airway flow (FEVl) to determine whether bronchial smooth muscle is also abnormal in microvascular angina. FEV1 was measured in 11 patients with microvascular angina before and after incremental doses of methacholine and compared to normal controls. Methacholine caused a 20% decrease in FEVl from baseline in 8 of 11 patients at a methacholine dose of 81 plus or minus 71 cumulative units. In contrast, only 2 of 12 control patients had a 20% decrease in FEV1 at a methacholine dose of 179 plus or minus cumulative units p less than .001) a response rate significantly less than patients with microvascular angina (p less than .02). Thus, dyspnea in microvascular angina patients may be due to hyperactivity of bronchial smooth muscle. These results further indicate a more generalized disorder of vascular and nonvascular smooth muscle function in this syndrome.